Calcineurin Inhibitors (CNI) use may be associated with progressive renal dysfunction. Clinical trials have shown that CNI minimization or discontinuation may aid in improvement in renal function. However, these studies have not answered the question “what is the extra mileage” that is obtained by this conversion; i.e. what is the amount of time that will progress before the renal function returns to its previous level.

We designed a retrospective, single center study of all cases in which patients were discontinued from a CNI based exclusively on biopsy proven CNI Toxicity / Interstitial fibrosis. Interstitial fibrosis was determined by using CADI scores. All patients were on CSA and Sirolimus (SRL) prior to CNI discontinuation. In all cases the CSA was substituted for mycophenolate mofetil. We determined renal function 1 year prior to conversion, at conversion and at six months post conversion. Patients were followed until their GFR returned to their pre-conversion level (the primary endpoint) or a minimum or 5 years. Patients expiring with a functioning graft or lost to follow-up were considered “intent-to-treat” and the event date was considered as having met the endpoint.

A total of 42 cases met the inclusion criteria. The average rate of GFR loss in the year leading to conversion was 15 ml/min (SD 12.9), a 31% loss in the GFR. Six months post conversion 80% of cases (34/42) showed improvement in the GFR. In the cohort showing improved GFR, the average increase in GFR was 8.93 ml/min (SD 6.61), a 32% increase in the GFR. 59% of cases (20/34) reached the primary endpoint. The average time to reach the endpoint was 3.25 years (SD 1.32). The remaining 41% of cases (14/34) had not reached the primary endpoint at a mean follow-up of 7.4 years (SD 1.46). Although the results of this study are in line with others in the literature we differ in the initial choice of an mTOR and CNI with subsequent conversion to an antimetabolite. Additionally we have a generous follow-up period allowing us to estimate a potential “length of effect” or mileage incurred by CNI discontinuation.

In patients with biopsy proven interstitial fibrosis leading renal dysfunction discontinuation of a CNI will result in improvements in GFR in 80% of patients at 6 months post intervention. In over half of cases, this intervention will provide at least an additional three years of “extra life” to the graft.

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